Department of Pathology
Harvard Medical School
77 Ave. Louis Pasteur
Boston, MA 02215
18 Postdoctoral Fellows, 4 Graduate Students
We explore how T cells differentiate into their different lineages and final effector states, particularly from the standpoint of self-tolerance and autoimmunity. Studies on autoimmunity explore the molecular and genetic failures of tolerance in diabetes, rheumatoid arthritis and in the disease that appears in Aire-deficient individuals. Major questions tackled are why thymic tolerance is defective in these models, what triggers the autoimmune processes, how their progression is regulated. We ask where and how regulatory “Treg” cells are generated and control autoimmune destruction in mouse models and in human patients.
Molecular investigations tackle how the Aire transcription factor controls the ectopic expression of self-antigens in the thymus, or how FoxP3 coordinates with other elements in specifying the different facets of the Treg phenotype. Our research involves many collaborations across the campus, and a wide range of technologies are applied to these questions (manipulation of the mouse germline, gene expression profiling, mass spectrometry, RNAi screens). Imaging tools are used to analyze and track autoimmune inflammation in vivo, in mice and human patients. The lab also has an interest in bioinformatic approaches to explore the regulation and connectivity of gene expression at the “Systems Immunology” level being one of the leads of the Immunological Genome explorations in mice and human cells (www.immgen.org).
Binstadt B, Pate P, Alencar H, Nigrovic P, Lee DM, Mahmood U, Weissleder R, Mathis D, and Benoist C. Particularities ofthe vasculature can promote the organ specificity of autoimmune attack. Nature Immunol. (2006), 7,284-92.
Hill J, Feuerer, M, Tash K, Haxhinasto S, Perez J, Melamed R, Mathis D and Benoist, C. Foxp3-dependent and independent regulation of the Treg transcriptional signature. Immunity,(2007), 27:786-800.
Heng TSP, Painter MW & the ImmGen Consortium. The Immunological Genome Project: an analytical workbench for gene-expression and regulatory networks in the immune system. Nat. Immunol. (2008), 9:1091-1094.
Feuerer M, Shen Y, Littman D, Benoist C and Mathis D. How punctual ablation of Foxp3+ T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity (2009), 31:654-656.
Abramson J, Giraud M, Benoist C and Mathis D. Aire's partners in the molecular control of immunological tolerance. Cell (2010), 140:123-135.
Immunology webpage updated 7/8/2010